Prognostic factors in patients with acute ischemic stroke treated with intravenous tissue plasminogen activator: The first study among Iranian patients.

Background: Tissue plasminogen activator (tPA) has been long approved as an efficacious treatment in patients with acute ischemic stroke (AIS); however, due to some serious complications, particularly intracranial hemorrhage (ICH), many physicians are still reluctant to use it liberally. This study sought to find potential prognostic factors in patients with AIS treated with tPA. Methods: A retrospective, hospital-bases observational study was conducted. Consecutively, a total of 132 patients with AIS treated with intravenous tPA, form June 2011 to July 2015 were enrolled. Inclusion and exclusion criteria were based on updated guidelines. Probable prognostic variables were examined separately in three distinct groups; the occurrence of ICH within 24 hours after treatment, poor 3-month outcome on the basis of modified Rankin Scale (mRS) and 3-month mortality. Results: Patients were 83 men (62.9%) and 49 women (37.1%) with a median age of 66 years [interquartile range (IQR)of 55-72]. Any type of hemorrhage, symptomatic hemorrhage [based on the European Cooperative Acute Stroke Study III (ECASS III) definition] within 24 hours posttreatment, poor 3-month outcome (mRS 3-6), and 3-month mortality were documented in 10.6%, 4.5%, 53.2%, and 23.6% of patients, respectively. Increased baseline blood glucose was a significant but dependent predictor of hemorrhage within the first 24 hours posttreatment. Dependent predictors of a 3-month poor outcome were high age, the National Institutes of Health Stroke Scale (NIHSS) at baseline, decreased admitting glomerular filtration rate (GFR), and the presence of atrial fibrillation (AF) rhythm, and ICH within 24 hours posttreatment. Only age [Odds ratio (OR) adjusted 1.05] and initial NIHSS (OR adjusted 1.23), however, were recognized as the independent variables in this regard. The only independent predictor of 3-month mortality was the initial NIHSS (OR adjusted 1.18). Conclusion: According to the findings of the present study, advanced age and high baseline NIHSS are two independent prognostic factors in patients with AIS treated with tPA.

separately in three distinct groups; the occurrence of ICH within 24 hours after treatment, poor 3-month outcome on the basis of modified Rankin Scale (mRS) and 3-month mortality. Results: Patients were 83 men (62.9%) and 49 women (37.1%) with a median age of 66 years [interquartile range (IQR)of 55-72]. Any type of hemorrhage, symptomatic hemorrhage [based on the European Cooperative Acute Stroke Study III (ECASS III) definition] within 24 hours posttreatment, poor 3-month outcome (mRS 3-6), and 3-month mortality were documented in 10.6%, 4.5%, 53.2%, and 23.6% of patients, respectively. Increased baseline blood glucose was a significant but dependent predictor of hemorrhage within the first 24 hours posttreatment. Dependent predictors of a 3-month poor outcome were high age, the National Institutes of Health Stroke Scale (NIHSS) at baseline, decreased admitting glomerular filtration rate (GFR), and the presence of atrial fibrillation (AF) rhythm, and ICH within 24 hours posttreatment. Only age [Odds

Iranian Journal of Neurology
Introduction High prevalence of stroke and related disability have great devastating impact on the health status of general population. 1 Providing immediate care in patients with cerebrovascular accidents could dramatically decrease associated consequences that usually cause permanent disability. Recent trials showed the superiority of endovascular therapy with a stent retriever to intravenous thrombolysis (IVT) in selected patients with acute ischemic stroke (AIS). [2][3][4][5][6] Nevertheless, in developing countries, especially, with the lack of facilities, IVT still is the only available effective pharmacologic approach in selected patients with AIS. [7][8][9] More than four fifths of stroke mortality in the world occur in developing countries. 10 In Iran, stroke occurs about ten years earlier in comparison to most developed countries and its prevalence is 23-139 per 100000 populations. [10][11][12] Noting the rapidly growing number of patients with stroke in our country and the need for studies focusing on potential prognostic factors in association with administration of tissue plasminogen activator (tPA) in such patients, the present work aimed to examine potential prognostic factors in Iranian patients with AIS who received intravenous tPA.

Materials and Methods
A total of 132 patients with AIS who received tPA in Tabriz Imam Reza teaching hospital, Iran, were enrolled in this retrospective hospital-bases observational study from January 2009 to March 2015. Inclusion and exclusion criteria were based on updated protocols published by the American Heart Association and the American Academy of Neurology. 13 Data on demographic profile, risk factors, blood pressure at hospital arrival, laboratory tests, brain computed tomography (CT) scans, severity of initial stroke as assessed using the National Institutes of Health Stroke Scale (NIHSS), time of symptoms onset, and time of recombinant tPA (rtPA) administration were recorded. Brain CT scans were done for all patients just before and 24 hours after the treatment, and the presence of any hemorrhage or symptomatic intracranial hemorrhage (SICH) were recorded. The European Cooperative Acute Stroke Study III (ECASS III) definition for SICH was used (any new evidence of intracranial blood on imaging accompanied by a neurological deterioration of four or more points on the NIHSS score from baseline).
Functional outcome at 3 months was assessed using the modified Rankin Scale (mRS). Patients who were unable to attend were interviewed by phone. Possible prognostic factors were examined in three categories of intracranial hemorrhage (ICH) within the first 24 hours, poor 3-month outcome (mRS of 3-6), and 3-month mortality.
Written informed consent was obtained from each patient, and the Ethics Committee of Tabriz University of Medical Sciences approved the protocol of this study.
Data were shown as mean ± standard deviation (SD), median interquartile range (IQR), and frequency (%). The SPSS software (version 22, IBM Corporation, Armonk, NY, USA) was used for data analysis. The Kolmogorov-Smirnov test was employed to analyze the distribution of quantitative variables. Independent sample t, Mann-Whitney U, chi-square, and Fisher's exact tests were used for analyses. The logistic regression analysis was used for multivariate study. The Kaplan-Meier plot was employed to examine survival. A P value of less than 0.05 was considered statistically significant.
Study variables are compared between patients with and without ICH within the first 24 hours in table 2. Accordingly, the admission blood glucose level was significantly higher in patients with intracranial bleeding.
Variables are compared between the two groups of with and without 3-month poor outcome in table 3. Accordingly, median age, mean baseline NIHSS, frequency of patients with atrial fibrillation (AF) rhythm, and frequency of patients with first 24-hour ICH were all significantly higher, and the baseline mean glomerular filtration rate (GFR) was significantly lower in patients with poor outcome. In multivariate study, however, only age [P = 0.04, Odds ratio (OR) = 1.05] and baseline NIHSS (P = 0.01, OR = 1.23) were independent predictors of 3-month poor outcome.
Predictors of 3-month mortality are set out in Table 4. Accordingly, median baseline NIHSS, previous AF rhythm, and the first 24-hour ICH significantly predicted mortality. The only independent predictor of 3-month mortality was the baseline NIHSS (P = 0.02, OR = 1.18).
The related Kaplan-Meier plot of 3-month survival is depicted in figure 1.

Discussion
In the present study, potential prognostic factors in patients with AIS who received tPA were assessed. Any type of hemorrhage and SICH the first 24-36 hours was documented in 10.6% and 4.5% of these patients, respectively. studies, the mortality rate varies between 10% and 40% in such patients, and the related predictors have been reported to be the severity of stroke, previous patient disability, past medical status, age, sex and symptom-to-treatment interval. 15,18,31,[37][38][39] One of suggested factors affecting the association between response to tPA treatment is racial differences. 40,41 Therefore, since the present study is the first one among Iranian population, which reports prognostic factors in AIS patients treated with tPA, the findings are unique but need to be confirmed in future studies.
Finally, despite the uniqueness of the present work among Iranians, a rather small sample size compared to some robust available reports in the literature should be acknowledged as a limitation; and this is an observational study and the associations reported in this article may not clarify the causations. Further studies with larger sample size are needed to better clarify prognostic factors in these patients.

Conclusion
According to the findings of the present study, advanced age and high baseline NIHSS are two independent prognostic factors in patients with AIS treated with intravenous (IVT) thrombolysis.

Conflict of Interests
The authors declare no conflict of interest in this study.